November 17, 2017

Cleveland Multiport Catheter Enhances Topotecan Delivery in High-Grade Glioma

Report from first-in-human study of new convection-enhanced delivery device

17-NEU-1159-Vogelbaum-650×450

The Cleveland Multiport Catheter (CMC), a novel four-port device for convection-enhanced delivery, successfully conveys high volumes of chemotherapy to enhancing and nonenhancing regions of recurrent high-grade gliomas. So conclude Cleveland Clinic researchers who presented results from a clinical trial in the first 12 patients treated with the device at the 2017 annual meeting of the Society for Neuro-Oncology in San Francisco.

Advertisement

Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy

“Breaking through the blood-brain barrier is a continuing major challenge for delivering therapeutic drugs to fight brain cancers,” says Cleveland Clinic neurosurgeon Michael A. Vogelbaum, MD, PhD, the study’s lead investigator. “We are very encouraged to see that our catheter can effectively deliver around the blood-brain barrier in the setting of both solid and infiltrative brain tumors.”

Dr. Vogelbaum is Associate Director of the Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center and Director of the Center for Translational Therapeutics and Professor of Surgery at Cleveland Clinic Lerner College of Medicine. He is one of the inventors of the CMC and leads the Cleveland Clinic team testing the device. He is founder and chief medical officer of Infuseon Therapeutics Inc., a Cleveland Clinic-owned spinoff company that is funding clinical development of the CMC. Dr. Vogelbaum’s roles in this development effort are covered under a Cleveland Clinic-approved conflict-of-interest management plan.

The CMC backstory

The CMC was granted FDA clearance in March 2017 as a therapeutic delivery device. While convection-enhanced delivery (CED) has been in investigational use for about 20 years, no drug has yet received FDA approval for direct delivery into the brain parenchyma.

The CMC, developed at Cleveland Clinic in partnership with Cleveland-based multinational manufacturer Parker Hannifin Corp., has several advantages over similar devices under investigation for CED:

  • While other devices have a single drug delivery catheter, the CMC has four microcatheters equally spaced around the tip of the CMC shaft through which drug can be delivered (see image at top of post), requiring fewer devices to cover a large volume of tissue.
  • The CMC can be placed in an operating room equipped with conventional neurosurgical guidance technology, avoiding the intraoperative MRI capabilities required by other delivery devices.
  • The CMC can be left in place for days (versus several hours for most other delivery devices), allowing delivery of more drug.

The CMC is surgically implanted and connected to low-rate infusion pumps. More details about the CMC are in this previous Consult QD post.

Advertisement

Study methods and findings

This study focused on recurrent high-grade glioma, a brain cancer that not only forms solid (enhancing) tumors but also grows in the brain in a highly infiltrative manner (nonenhancing), making it particularly resistant to radiation therapy and surgical excision. The study involved two pilot trials:

  • Drug delivery was evaluated in both enhancing tumor and tumor-infiltrated brain (3 patients).
  • Drug delivery was evaluated in tumor-infiltrated brain after resection of the enhancing tumor (9 patients).

In both trials, two agents were delivered simultaneously through the CMC:

  • Topotecan, a standard chemotherapeutic agent used to treat lung and colon cancers. Although topotecan has demonstrated effectiveness against glioma in cell cultures, it cannot cross the blood-brain barrier under conventional delivery methods and consequently has not been effective when given by its conventional intravenous route of delivery.
  • A gadolinium tracer (gadolinium DTPA) visible on MRI. It was used to detect distribution and thereby evaluate the efficacy of drug delivery.

All 12 patients underwent successful placement of two CMCs each and completed infusions ranging from 48 to 96 hours. All catheters were placed with conventional operating room technology. MRI was performed intermittently during infusion.

Large differences were found in the volumes of distribution based on the site of delivery, with the highest volumes delivered to tumor-infiltrated regions (25-92 mL). No obvious backflow into the CMC shaft was observed intra- or perioperatively. No hemorrhages occurred during catheter placement or removal.

Next steps

Dr. Vogelbaum’s team is currently recruiting patients for a third trial that will focus on optimizing the use of the CMC to deliver to the enhancing (solid) portion of recurrent tumors. They are also developing additional new devices for both short- and long-term delivery of therapeutics to the brain.

Advertisement

The CMC is not limited to delivery of chemotherapies. It is designed to be capable of delivering other biologic and cellular therapies to the brain, for brain tumors and also for other neurological conditions such as Alzheimer’s disease, Parkinson’s disease and epilepsy.

Dr. Vogelbaum notes that the CMC also could potentially be used to deliver therapeutics to solid tumors elsewhere in the body. Localized delivery could potentially avoid complications such as the bone marrow toxicity seen with typical systemic administration of many chemotherapies.

“The CMC has demonstrated excellent promise in our initial trials,” he says. “Successful localized and locoregional delivery is critical to treating brain tumors and a multitude of other conditions as well.”

Related Articles

Cleveland Clinic physiatrist
March 22, 2024
The Vital Role of Oncology Rehabilitation (Podcast)

New program provides prehabilitation and rehabilitation services to help patients with cancer maintain and regain function

Doctors working on MGUS screening study
March 18, 2024
Pilot Study Aims for Early Identification of Multiple Myeloma Precursor Among Black Patients

First-of-its-kind research investigates the viability of standard screening to reduce the burden of late-stage cancer diagnoses

Hematologist at Cleveland Clinic
March 14, 2024
Advances in Mantle Cell Lymphoma Treatment (Podcast)

Global R&D efforts expanding first-line and relapse therapy options for patients

Physician with patient
March 6, 2024
Targeting Uncontrolled Erythrocytosis in Polycythemia Vera with Rusfertide

Study demonstrates ability to reduce patients’ reliance on phlebotomies to stabilize hematocrit levels

Dr. Jagadeesh at Cleveland Clinic
February 28, 2024
Treating Patient with Systemic T-Cell Lymphoma and Graft-Versus-Host Disease

A case study on the value of access to novel therapies through clinical trials

Doctor measuring patient's waist size
February 26, 2024
Impact of Obesity on GVHD & Transplant Outcomes in Hematologic Malignancies

Findings highlight an association between obesity and an increased incidence of moderate-severe disease

Physician with patient
February 21, 2024
Strategies for Improving Clinical Trial Equity

Cleveland Clinic Cancer Institute takes multi-faceted approach to increasing clinical trial access

How antibody drug conjugates work
February 13, 2024
Real-World Use of Trastuzumab Deruxtecan

Key learnings from DESTINY trials

Ad